PAMAM-D纳米载体介导TF反义寡脱氧核苷酸防治心肌缺血再灌注损伤的实验研究

摘要

Objective To observe the effect of polyamidoamine dendrimers (PAMAM-D) mediated antisense oligodeoxynucleotide against tissue factor (TF) on myocardial ischemia-reperfusion injury in rats.Methods Antisense oligodeoxynucleotide against TF (AS/TF), sense oligodeoxynucleotide against TF (S/TF)and scrambled oligodeoxynucleotide (Sc/TF) were designed and synthesized respectively, which were coupled with PAMAM-D nanometer vector and formed oligodeoxynucleotide-PAMAM-D polymer. 100 male Lewis rats were randomly divided into sham operation group, ischemia-reperfusion group, AS/TF intervention group, S/TF control group and Sc/TF control group. Results 90 min after ischemia and at the end of reperfusion, the concentrations of TnT and TAT increased significantly ( P＜0.05 or P＜ 0.01 ) ,as compared with those in sham operation group,however,the levels in AS/TF intervention group were much lower than those in the other 3 ischemia-reperfusion injury groups ( P ＜ 0. 05 or P ＜ 0. 01 ). After reperfnsion, the transcription and expression of TF gene in myocardial cells of the infarction and ischemic zone were obviously enhanced in ischemia-reperfusion injury groups ( P ＜ 0. 05 or P ＜ 0.01 ), as compared with those in sham operation group, however, which were improved in AS/TF intervention group, as compared with those in the other 3 ischemia-reperfusion groups ( P ＜ 0. 01 ). Conclusion By antagonizing the transcription and expression of TF, polyamidoamine dendrimers nanometer vector mediated antisense oligodeoxynucleotide which has protective effect on myocardial ischemia-reperfusion injury.%目的 研究聚酰胺-胺型树枝状高聚物(PAMAM-D)纳米载体介导组织因子(TF)反义寡脱氧核苷酸对大鼠心肌缺血再灌注损伤的作用.方法 分别设计合成针对大鼠TF的反义寡脱氧核苷酸(AS/TF)、正义寡脱氧核苷酸(S/TF)和错配寡脱氧核苷酸(Sc/TF),将该三种寡脱氧核苷酸偶联于PAMAM-D纳米载体,构建寡核苷酸-PAMAM-D的聚合物.将100只雄性Lewis大鼠随机等分为假手术组、缺血再灌注组、AS/TF防治组、S/TF对照组和Sc/TF对照组.结果 心肌缺血90 min及再灌注3 h后,各组大鼠血液中的TnT和TAT均显著增多(与假手术组相比,P＜0.05或＜0.01),而AS/TF防治组大鼠血液中的TnT和TAT均明显低于其他3个缺血再灌注组(P＜0.05或＜0.01).心肌缺血再灌注3 h后,缺血再灌注的各组大鼠梗死区及边缘区心肌组织中TF基因的转录和表达均强于假手术组(与假手术组相比,P＜0.05或＜0.01),而AS/TF防治组大鼠梗死区及边缘区心肌组织中TF基因的转录和表达则较其他3个缺血再灌注组明显减弱(P＜0.01).结论 聚酰胺-胺型树枝状高聚物纳米载体介导的TF反义寡脱氧核苷酸对心肌缺血再灌注损伤有明显的保护作用.